This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH or CH2 groups of donor with a disulfide as acceptor. The systematic name of this enzyme class is 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone:oxidized-dithi othreitol oxidoreductase.

1.
Chemical reaction
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A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Nuclear chemistry is a sub-discipline of chemistry that involves the reactions of unstable. The substance initially involved in a reaction are called reactants or reagents. Chemical reactions are characterized by a chemical change, and they yield one or more products. Reactions often consist of a sequence of individual sub-steps, the elementary reactions. Chemical reactions are described with chemical equations, which present the starting materials, end products. Chemical reactions happen at a characteristic reaction rate at a given temperature, typically, reaction rates increase with increasing temperature because there is more thermal energy available to reach the activation energy necessary for breaking bonds between atoms. Reactions may proceed in the forward or reverse direction until they go to completion or reach equilibrium, Reactions that proceed in the forward direction to approach equilibrium are often described as spontaneous, requiring no input of free energy to go forward. Non-spontaneous reactions require input of energy to go forward. Different chemical reactions are used in combinations during chemical synthesis in order to obtain a desired product, in biochemistry, a consecutive series of chemical reactions form metabolic pathways. These reactions are catalyzed by protein enzymes. Chemical reactions such as combustion in fire, fermentation and the reduction of ores to metals were known since antiquity, in the Middle Ages, chemical transformations were studied by Alchemists. They attempted, in particular, to lead into gold, for which purpose they used reactions of lead. The process involved heating of sulfate and nitrate minerals such as sulfate, alum. In the 17th century, Johann Rudolph Glauber produced hydrochloric acid and sodium sulfate by reacting sulfuric acid, further optimization of sulfuric acid technology resulted in the contact process in the 1880s, and the Haber process was developed in 1909–1910 for ammonia synthesis. From the 16th century, researchers including Jan Baptist van Helmont, Robert Boyle, the phlogiston theory was proposed in 1667 by Johann Joachim Becher. It postulated the existence of an element called phlogiston, which was contained within combustible bodies. This proved to be false in 1785 by Antoine Lavoisier who found the explanation of the combustion as reaction with oxygen from the air

2.
Alcohol dehydrogenase
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In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+. Early on in evolution, a method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time. Gene duplication of ADH-3, followed by series of mutations, the other ADHs evolved, the ability to produce ethanol from sugar is believed to have initially evolved in yeast. Since rotting fruit can contain more than 4% of ethanol, animals eating the fruit needed a system to metabolize exogenous ethanol. This was thought to explain the conservation of ethanol active ADH in other species than yeast, in the Histidine variant, the enzyme is much more effective at the aforementioned conversion. In humans, various haplotypes arising from this mutation are more concentrated in regions near Eastern China, in regions where rice was cultivated, rice was also fermented into ethanol. The results of increased alcohol availability led to alcoholism and abuse by those able to acquire it and those with the variant allele have little tolerance for alcohol, thus lowering chance of dependence and abuse. Classical Darwinian evolution would act to select against the form of the enzyme because of the lowered reproductive success of individuals carrying the allele. The result would be a frequency of the allele responsible for the His-variant enzyme in regions that had been under selective pressure the longest. The first-ever isolated alcohol dehydrogenase was purified in 1937 from Saccharomyces cerevisiae, many aspects of the catalytic mechanism for the horse liver ADH enzyme were investigated by Hugo Theorell and coworkers. ADH was also one of the first oligomeric enzymes that had its amino acid sequence, in early 1960, it was discovered in fruit flies of the genus Drosophila. In mammals this is a reaction involving the coenzyme nicotinamide adenine dinucleotide. The mechanism in yeast and bacteria is the reverse of this reaction and these steps are supported through kinetic studies. The substrate is coordinated to the zinc and this enzyme has two atoms per subunit. One is the site, which is involved in catalysis. In the active site, the ligands are Cys-46, Cys-174, His-67, the other subunit is involved with structure. In this mechanism, the hydride from the alcohol goes to NAD+, crystal structures indicate that the His-51 deprotonates the nicotinamide ribose, which deprotonates Ser-48. Finally, Ser-48 deprotonates the alcohol, making it an aldehyde, from a mechanistic perspective, if the enzyme adds hydride to the re face of NAD+, the resulting hydrogen is incorporated into the pro-R position

3.
Isocitrate dehydrogenase
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Isocitrate dehydrogenase and is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate and CO2. This is a process, which involves oxidation of isocitrate to oxalosuccinate, followed by the decarboxylation of the carboxyl group beta to the ketone. In humans, IDH exists in three isoforms, IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and they localize to the cytosol as well as the mitochondrion and peroxisome. All the known NADP-IDHs are homodimers, most isocitrate dehydrogenases are dimers, to be specific, homodimers. In comparing C. glutamicum and E. coli, monomer and dimer, respectively, however, C. glutamicum was recorded as having ten times as much activity than E. coli and seven times more affinitive/specific for NADP. C. glutamicum favored NADP+ over NAD+, in terms of stability with response to temperature, both enzymes had a similar Tm or melting temperature at about 55 °C to 60 °C. However, the monomer C. glutamicum showed a more consistent stability at higher temperatures, the dimer E. coli showed stability at a higher temperature than normal due to the interactions between the two monomeric subunits. The structure of Mycobacterium tuberculosis ICDH-1 bound with NADPH and Mn bound has been solved by X-ray crystallography and it is a homodimer in which each subunit has a Rossmann fold, and a common top domain of interlocking β sheets. Mtb ICDH-1 is most structurally similar to the R132H mutant human ICDH found in glioblastomas, similar to human R132H ICDH, Mtb ICDH-1 also catalyzes the formation of α-hydroxyglutarate. The reaction is stimulated by the mechanisms of substrate availability, product inhibition. Within the citric cycle, isocitrate, produced from the isomerization of citrate. Using the enzyme isocitrate dehydrogenase, isocitrate is held within its site by surrounding arginine, tyrosine, asparagine, serine, threonine. The first box shows the overall isocitrate dehydrogenase reaction, the reactants necessary for this enzyme mechanism to work are isocitrate, NAD+/NADP+, and Mn2+ or Mg2+. The products of the reaction are alpha-ketoglutarate, carbon dioxide, water molecules are used to help deprotonate the oxygens of isocitrate. The second box is Step 1, which is the oxidation of the alpha-C, oxidation is the first step that isocitrate goes through. The third box is Step 2, which is the decarboxylation of oxalosuccinate, in this step, the carboxyl group oxygen is deprotonated by a nearby Tyrosine amino acid and those electrons flow down to carbon 2. The lone pair on the alpha-C oxygen picks up a proton from a nearby Lysine amino acid, the fourth box is Step 3, which is the saturation of the alpha-beta unsaturated double bond between carbons 2 and 3

4.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms

5.
Glycerol-3-phosphate dehydrogenase
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Glycerol-3-phosphate dehydrogenase is an enzyme that catalyzes the reversible redox conversion of dihydroxyacetone phosphate to sn-glycerol 3-phosphate. Glycerol-3-phosphate dehydrogenase serves as a link between carbohydrate metabolism and lipid metabolism. It is also a contributor of electrons to the electron transport chain in the mitochondria. Older terms for glycerol-3-phosphate dehydrogenase include alpha glycerol-3-phosphate dehydrogenase and glycerolphosphate dehydrogenase, however, glycerol-3-phosphate dehydrogenase is not the same as glyceraldehyde 3-phosphate dehydrogenase, whose substrate is an aldehyde not an alcohol. GPDH plays a role in lipid biosynthesis. Through the reduction of dihydroxyacetone phosphate into glycerol 3-phosphate, GPDH allows the prompt dephosphorylation of glycerol 3-phosphate into glycerol, additionally, GPDH is responsible for maintaining the redox potential across the inner mitochondrial membrane in glycolysis. The NAD+/NADH coenzyme couple act as a reservoir for metabolic redox reactions. Most of these reactions occur in the mitochondria. To regenerate NAD+ for further use, NADH pools in the cytosol must be reoxidized, since the mitochondrial inner membrane is impermeable to both NADH and NAD+, these cannot be freely exchanged between the cytosol and mitochondrial matrix. Simultaneously, NADH is oxidized to NAD+ in the reaction, As a result. GPD1 consists of two subunits, and reacts with dihydroxyacetone phosphate and NAD+ though the interaction, Figure 4. The phosphate group of DHAP is half-encircled by the side-chain of Arg269, the conserved residues Lys204, Asn205, Asp260 and Thr264 form a stable hydrogen bonding network. The other hydrogen bonding network includes residues Lys120 and Asp260, as well as a water molecule. In these two networks, only the ε-NH3+ group of Lys204 is the nearest to the C2 atom of DHAP. GPD2 consists of 4 identical subunits, studies indicate that GPDH is mostly unaffected by pH changes, neither GPD1 or GPD2 is favored under certain pH conditions. At high salt concentrations, GPD1 activity is enhanced over GPD2, changes in temperature do not appear to favor neither GPD1 nor GPD2. The cytosolic together with the mitochondrial glycerol-3-phosphate dehydrogenase work in concert, oxidation of cytoplasmic NADH by the cytosolic form of the enzyme creates glycerol-3-phosphate from dihydroxyacetone phosphate. As a result, there is a net loss in energy, the combined action of these enzymes maintains the NAD+/NADH ratio that allows for continuous operation of metabolism

6.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase

7.
Nicotinamide adenine dinucleotide
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Nicotinamide adenine dinucleotide is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups, one nucleotide contains an adenine base and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively, in metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The coenzyme is, therefore, found in two forms in cells, NAD+ is an oxidizing agent – it accepts electrons from other molecules and becomes reduced and this reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the function of NAD. However, it is used in other cellular processes, the most notable one being a substrate of enzymes that add or remove chemical groups from proteins. Because of the importance of these functions, the involved in NAD metabolism are targets for drug discovery. In organisms, NAD can be synthesized from simple building-blocks from the amino acids tryptophan or aspartic acid, in an alternative fashion, more complex components of the coenzymes are taken up from food as the vitamin called niacin. Similar compounds are released by reactions that break down the structure of NAD and these preformed components then pass through a salvage pathway that recycles them back into the active form. Some NAD is also converted into nicotinamide adenine dinucleotide phosphate, the chemistry of this related coenzyme is similar to that of NAD, nicotinamide adenine dinucleotide, like all dinucleotides, consists of two nucleosides joined by a pair of bridging phosphate groups. The nucleosides each contain a ring, one with adenine attached to the first carbon atom. The nicotinamide moiety can be attached in two orientations to this carbon atom. Because of these two structures, the compound exists as two diastereomers. It is the diastereomer of NAD+ that is found in organisms. These nucleotides are joined together by a bridge of two groups through the 5 carbons. In metabolism, the compound accepts or donates electrons in redox reactions, such reactions involve the removal of two hydrogen atoms from the reactant, in the form of a hydride ion, and a proton. The proton is released into solution, while the reductant RH2 is oxidized, the midpoint potential of the NAD+/NADH redox pair is −0.32 volts, which makes NADH a strong reducing agent. The reaction is reversible, when NADH reduces another molecule and is re-oxidized to NAD+

8.
L-xylulose reductase
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Dicarbonyl/L-xylulose reductase, also known as carbonyl reductase II, is an enzyme that in human is encoded by the DCXR gene located on chromosome 17. The DCXR gene encodes a protein that is approximately 34 kDa in size. The protein is expressed in the kidney and localizes to the cytoplasmic membrane. DCSR catalyzes the reduction of several L-xylylose as well as a number of pentoses, tetroses, trioses and this enzyme belongs to the superfamily of short-chain oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this class is xylitol, NADP+ 2-oxidoreductase. A deficiency is responsible for pentosuria, the insufficiency of L-xylulose reductase activity causes an inborn error of metabolism disease characterized by excessive urinary excretion of L-xylulose. Over-expression and ectopic expression of the protein may be associated with prostate adenocarcinoma, L-xylulose reductase at the US National Library of Medicine Medical Subject Headings

9.
Malate dehydrogenase
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Malate dehydrogenase is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of metabolic pathways, including the citric acid cycle. Other malate dehydrogenases, which have other EC numbers and catalyze other reactions oxidizing malate, have qualified names like malate dehydrogenase, several isozymes of malate dehydrogenase exist. There are two main isoforms in eukaryotic cells, one is found in the mitochondrial matrix, participating as a key enzyme in the citric acid cycle that catalyzes the oxidation of malate. Humans and most other mammals express the following two malate dehydrogenases, The malate dehydrogenase family contains L-lactate dehydrogenase and L-2-hydroxyisocaproate dehydrogenases, L-lactate dehydrogenases catalyzes the conversion of L-lactate to pyruvate, the last step in anaerobic glycolysis. The N-terminus is a Rossmann NAD-binding fold and the C-terminus is an unusual alpha+beta fold, in most organisms, malate dehydrogenase exists as a homodimeric molecule and is closely related to lactate dehydrogenase in structure. It is a protein molecule with subunits weighing between 30 and 35 kDa. Based on the amino acid sequences, it seems that MDH has diverged into two main groups that closely resemble either mitochondrial isozymes or cytoplasmic/chloroplast isozymes. The amino acid sequences of archaeal MDH are more similar to that of LDH than that of MDH of other organisms and this indicates that there is a possible evolutionary linkage between lactate dehydrogenase and malate dehydrogenase. Each subunit of the malate dehydrogenase dimer has two domains that vary in structure and functionality. A parallel β-sheet structure makes up the NAD+ binding domain, while four β-sheets, the subunits are held together through extensive hydrogen-bonding and hydrophobic interactions. Malate dehydrogenase has also shown to have a mobile loop region that plays a crucial role in the enzymes catalytic activity. Studies have also indicated that this region is highly conserved in malate dehydrogenase. The active site of malate dehydrogenase is a cavity within the protein complex that has specific binding sites for the substrate and its coenzyme. In its active state, MDH undergoes a change that encloses the substrate to minimize solvent exposure. The three residues in particular that comprise a catalytic triad are histidine, aspartate, both of work together as a proton transfer system, and arginines, which secure the substrate. Mechanistically, malate dehydrogenase catalyzes the oxidation of the group of malate by utilizing NAD+ as an electron acceptor. This oxidation step results in the elimination of a proton and an ion from the substrate

10.
DXP reductoisomerase
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DXP reductoisomerase is an enzyme that interconverts 1-deoxy-D-xylulose 5-phosphate and 2-C-methyl-D-erythritol 4-phosphate. It is classified under EC1.1.1.267 and it is part of the nonmevalonate pathway, and it is inhibited by fosmidomycin. It is normally abbreviated DXR, but it is sometimes named IspC and this enzyme is responsible for terpenoid biosynthesis in some organisms. In Arabidopsis thaliana 1-deoxy-D-xylulose 5-phosphate reductoisomerase is the first committed enzyme of the pathway for isoprenoid biosynthesis. The enzyme requires Mn2+, Co2+ or Mg2+ for activity, with Mn2+ being most effective

11.
Sorbitol dehydrogenase
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Sorbitol dehydrogenase is a cytosolic enzyme. In humans this protein is encoded by the SORD gene, sorbitol dehydrogenase is an enzyme in carbohydrate metabolism converting sorbitol, the sugar alcohol form of glucose, into fructose. Together with aldose reductase, it provides a way for the body to produce fructose from glucose without using ATP, sorbitol dehydrogenase uses NAD+ as a cofactor, its reaction is sorbitol + NAD+ --> fructose + NADH + H+. A zinc ion is involved in catalysis. Organs that use it most frequently include the liver and seminal vesicle, the structure of human sorbitol dehydrogenase was determined through crystallization experiments and X-ray diffraction. MolProbity Ramachandran analysis was conducted by Lovell, Davis, et al, the results were that 97. 1% of all residues were in favored regions and 100. 0% of all residues were in allowed regions, with no outliers. All four chains have 356 residues each and a catalytic site, the catalytic sites contain both a serine and a histidine residue, which are hydrophilic sidechains. The residues require NAD+ and an ion to be present for catalytic activity. Sorbitol dehydrogenase belongs to the family, which means that it helps catalyze oxidation reduction reactions. As stated above, the helps in the pathway of converting glucose into fructose. The interactions between subunits forming a tetramer in SDH is determined by non-covalent interaction and these non-covalent interactions consists of an hydrophobic effect, hydrogen bonds, and electrostatic interactions between the four identical subunits. For homotetrameric proteins such as SDH, the structure is believed to have evolved going from a monomeric to a dimeric, the SDH proteins have a close evolutionary relationship with alcohol dehydrogenase, which also belongs to the protein superfamily of medium-chain dehydrogenase/reductase enzymes. Mammalian ADHs are all dimeric enzymes but certain bacterial ADHs also share a tetrameric quaternary structure, the general binding process in SDH is described by the gain in free energy, which can be determined from the rate of association and dissociation between subunits. A hydrogen-bonding network between subunits has been shown to be important for the stability of the tetrameric quaternary protein structure. In tissues where sorbitol dehydrogenase is low or absent, such as in the retina, lens, kidney, in uncontrolled diabetes, large amounts of glucose enter these tissues and is then converted to sorbitol by aldose reductase. Sorbitol then accumulates, causing water to be drawn into the due to the increased osmotic pressure. Retinopathy, cataract formation, nephropathy, and peripheral neuropathy seen in diabetes are partly due to this phenomenon

12.
3-hydroxyacyl-CoA dehydrogenase
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This enzyme belongs to the family of oxidoreductases, to be specific those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. It is involved in fatty acid metabolic processes. Specifically it catalyzes the third step of oxidation, the oxidation of L-3-hydroxyacyl CoA by NAD+. The reaction converts the hydroxyl group into a keto group, the end product is 3-ketoacyl CoA. This enzyme participates in 8 metabolic pathways, The systematic name of this class is -3-hydroxyacyl-CoA

The energies of the stages of a chemical reaction. Uncatalysed (dashed line), substrates need a lot of activation energy to reach a transition state, which then decays into lower-energy products. When enzyme catalysed (solid line), the enzyme binds the substrates (ES), then stabilizes the transition state (ES‡) to reduce the activation energy required to produce products (EP) which are finally released.

Malate dehydrogenase (EC 1.1.1.37) (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate …

Structure of the protein with attached cofactors

Image: General Malate Dehydrogenase Catalyzed Reaction

3-D crystal structure of the mobile loop region in malate dehydrogenase in the closed and open conformation. The MDH closed conformation is shown in pink (indicated by the pink arrow) while the open conformation is shown in cyan (indicated by the cyan arrow).